Evidence map›Paper›PMID 31611694›Full record

ArticleNature methods2019

Machine learning-guided channelrhodopsin engineering enables minimally invasive optogenetics.

Claire N Bedbrook, Kevin K Yang, J Elliott Robinson, Elisha D Mackey, Viviana Gradinaru, Frances H Arnold

Abstract read
In one paragraph

Article in Nature methods, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

104 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Efficient, Few-shot Directed Evolution with Energy Rank Alignment.bioRxiv : the preprint server for biology · 2026
    Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Optogenetic engineering for ion channel modulation.Current opinion in chemical biology · 2025
    Review
  13. Article
  14. Article
  15. Review
  16. Sensing a rainbow of colors: algal photoreceptors.Frontiers in plant science · 2025
    Review
  17. Protein design accelerates the development and application of optogenetic tools.Computational and structural biotechnology journal · 2025
    Review
  18. Discovery of Therapeutic Antibodies Targeting Complex Multi-Spanning Membrane Proteins.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024
    Review
  19. Article
  20. Article

44 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Claire N BedbrookDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0003-3973-598X
Kevin K Yang *Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.
J Elliott Robinson *Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0001-9417-3938
Elisha D MackeyDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Viviana GradinaruDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. viviana@caltech.edu.ORCID http://orcid.org/0000-0001-5868-348X
Frances H ArnoldDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. fha@cheme.caltech.edu.ORCID http://orcid.org/0000-0002-4027-364X

Funding

Comprehensive Structural and Functional Mapping of the Mammalian Cardiac Nervous SystemOT2OD023848 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI EFIMOV, IGOR R, FOWLKES, CHARLESS · 2016 to 2021
$21.4M
Circuit-Specific Delivery of Large Cargo Across the Nervous Systems of Adult Mammals and Embryos via Novel Engineered Systemic VectorsDP1NS111369 · NINDS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI GRADINARU, VIVIANA · 2018 to 2023
$5.9M
Neuromodulation and Neurodegeneration: the Missing Link and Mechanisms of ActionDP2NS087949 · NINDS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI GRADINARU, VIVIANA · 2013 to 2019
$4.1M
Noninvasive Gene Delivery for Monitoring and Perturbing Cell Types and Circuits in Transgenic and Non-Transgenic AnimalsRF1MH117069 · NIMH · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI GRADINARU, VIVIANA · 2018 to 2018
$2.3M
Opsineering: Engineering Novel ChannelRhodospins for Optogenetics ApplicationsF31MH102913 · NIMH · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI BEDBROOK, CLAIRE NICOLE · 2014 to 2016
$110k
NIH HHS OT2 OD023848NIMH NIH HHS F31 MH102913NIMH NIH HHS RF1 MH117069NINDS NIH HHS DP1 NS111369NINDS NIH HHS DP2 NS087949
6 · The paper itself

Abstract

We engineered light-gated channelrhodopsins (ChRs) whose current strength and light sensitivity enable minimally invasive neuronal circuit interrogation. Current ChR tools applied to the mammalian brain require intracranial surgery for transgene delivery and implantation of fiber-optic cables to produce light-dependent activation of a small volume of tissue. To facilitate expansive optogenetics without the need for invasive implants, our engineering approach leverages the substantial literature of ChR variants to train statistical models for the design of high-performance ChRs. With Gaussian process models trained on a limited experimental set of 102 functionally characterized ChRs, we designed high-photocurrent ChRs with high light sensitivity. Three of these, ChRger1-3, enable optogenetic activation of the nervous system via systemic transgene delivery. ChRger2 enables light-induced neuronal excitation without fiber-optic implantation; that is, this opsin enables transcranial optogenetics.

Indexed as

Machine LearningOptogeneticsAnimalsChannelrhodopsinsHEK293 CellsHumansMiceMice, Inbred C57BLProtein EngineeringChannelrhodopsins

Identifiers

PMID31611694
PMCPMC6858556

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.